tbuckley/cabot-search huggingface dataset:
Analysis of patient-physician portal secure message content and the associated cost savings in oncology practice.
Authors: Brandon Anderson, Liisa Lyon, Michael Jisoo Lee, Deepika Kumar, Elad Neeman, Ali Duffens, Dinesh Kotak, Hongxin Sun, Mary Reed, Raymond Liu
Journal: Journal of Clinical Oncology (2023)

1503 Background: The consistent utilization of secure messaging (“SM”) since the onset of the COVID-19 pandemic has provided cancer patients with unprecedented access to their medical providers, resulting in reduced out-of-pocket costs for patients at the expense of increased workload for oncologists. Herein we analyze oncology SM content and report estimated cost savings from reduced traditional clinic visits. Methods: This population-based retrospective cohort study examined the content of patient-initiated SM threads exchanged through the patient portal website or app over a one-year period (6/1/21 to 5/31/22) at 22 Kaiser Permanente Northern California Oncology practices. A trained physician researcher reviewed a random sample of 500 SM threads and categorized them by message content type, acuity, and appropriate level of service. Standard costs were applied using the average of 2021 and 2022 Center for Medicare Services physician fee schedule and US patient average specialty copayment. Results: During the study period, 49,230 patients initiated 398,835 unique SM threads to 238 oncology providers. The average number of replies to patients’ initial messages was 2.6, with a mode of 1 (maximum 36). Of the SM threads reviewed, only 28.0% required oncologist expertise. Based on thread content, the remaining 72.0% may have been better managed by a nurse (35.4%), medical assistant (29.2%), primary care doctor (6.2%), or a different subspecialty provider (1.2%). Emergency care was required in 2.8% of the total threads reviewed. Significant medical care was provided to patients in 26.0% of the total SM threads which would traditionally require a billable visit (i.e., in-person, telephone, or video). We estimate that these clinical actions may represent 4,299,281.77 of savings in medical care (based on traditional 10-19-minute visits), and 4,562,672.40 in potentially avoided out-of-pocket co-pay costs for patients. Conclusions: Increased utilization of remote medical care and specifically SM has recently generated additional workload for oncologists that may have been more appropriately managed by alternative providers. The magnitude of unreimbursed medical care provided via SM and the use of SM by cancer patients for emergent medical situations creates an urgent need for new models to assist with practice management. An alternative architecture for triaging, managing, and billing SM that utilizes artificial intelligence, machine learning algorithms, or medical assistants, nurses, and other providers could help manage the burden experienced by oncologists.
Clinical activity of camizestrant, a next-generation SERD, versus fulvestrant in patients with a detectable <i>ESR1</i> mutation: Exploratory analysis of the SERENA-2 phase 2 trial.
Authors: Mafalda Oliveira, Denys Pominchuk, Erika P. Hamilton, Yaroslav Kulyaba, Tamar Melkadze, Patrick Neven, Gia Nemsadze, Timur Andabekov, Yuriy Semegen, Yevhen Hotko, Claudio Zamagni, Vladimir Vladimirov, Maxine Bennett, Carmela Ciardullo, Teresa Klinowska, Justin P O Lindemann, Robert McEwen, Christopher J. Morrow, Ekaterine Arkania
Journal: Journal of Clinical Oncology (2023)

1066 Background: Camizestrant, a next-generation oral selective estrogen receptor antagonist and degrader (ngSERD), was compared at two dose levels to fulvestrant 500 mg (F) in post-menopausal women with advanced ER+, HER2˗ breast cancer with disease recurrence or progression after ≤1 endocrine therapy in the advanced setting in the Phase 2 randomized SERENA-2 study (NCT04214288). Camizestrant demonstrated statistically significant and clinically meaningful benefit vs F in progression-free survival (PFS) in the overall study population (Oliveira M et al. SABCS 2022 Annual Meeting. Abstract GS3-02.). Methods: Baseline circulating tumour DNA was collected at screening and/or Cycle 1 Day 1 and analysed by next-generation sequencing. A post hoc exploratory analysis compared investigator assessed PFS with camizestrant (data from 75 and 150 mg combined) vs F in patients with detectable baseline ESR1 (the gene that encodes ERα) hotspot mutations ( ESR1m). Patients were divided into subgroups based on whether 1 or &gt;1 ESR1m variants were detected, the specific ESR1m, and whether mutations were detected in BRCA1/2 or the MAPK pathway. The most prevalent mutations are presented. A Cox proportional hazards model was used to compare PFS. Results: 48/147 (32.7%) patients treated with camizestrant and 35/73 (47.9%) treated with F had a detectable ESR1m in at least 1 baseline sample. ESR1m were detected in 6/9 (67%) patients with a BRCA1/2 mutation and 5/26 (19%) with a MAPK pathway alteration; however, the numbers were too small to analyse efficacy in these subgroups. Conclusions: Camizestrant showed improved outcome vs F in patients with a detectable ESR1m at baseline and in the subgroups tested. The greatest median PFS improvement was seen in patients where a single ESR1m variant was detected, suggesting that early intervention upon detection of an ESR1m may provide the maximum patient benefit for camizestrant, a hypothesis that is being tested in the SERENA-6 clinical trial (NCT04964934). Clinical trial information: NCT04214288 . [Table: see text]
Real world treatment patterns and survival by germline BRCA (gBRCA) mutation status in patients with HER2-negative early breast cancer (eBC) in the US community oncology setting: A retrospective observational study.
Authors: Jay C. Andersen, Jagadeswara Rao Earla, Nicole Fulcher, Juliet Ndukum, Nicholas J. Robert, Mark E. Robson, Weiyan Li, Jamie Mejia
Journal: Journal of Clinical Oncology (2023)

e12535 Background: Germline BRCA mutations (gBRCAm) are associated with a higher risk of breast cancer at a younger age. Generally, gBRCA gene testing is performed in patients perceived as high risk for gBRCAm. Olaparib, a targeted poly (ADP-ribose) polymerase inhibitor (PARPi), has significantly improved overall survival (OS) in the randomized, double-blind OlympiA trial of patients with HER2-negative gBRCAm and was subsequently approved for the adjuvant treatment of patients with gBRCAm HER2-negative high-risk early breast cancer (eBC) treated with neoadjuvant or adjuvant chemotherapy. This study examines the real-world patient characteristics, treatment patterns and OS by gBRCA status among patients with HER2-negative eBC in a US community oncology setting prior to olaparib US approval for treatment of eBC. Methods: This retrospective observational study used structured data from The US Oncology Network's iKnowMed database. Adult patients were included if diagnosed with HER2-negative eBC (stage I-III) and if they initiated systemic neoadjuvant or adjuvant therapy between January 1, 2012-December 31, 2018 (followed through December 31, 2021). Patients were excluded if they progressed to stage IV within 6 months after neoadjuvant treatment or were diagnosed with another primary cancer. Descriptive analyses assessed patient characteristics, early-stage systemic treatments and OS among patients by gBRCA status. Results: Among 19,258 patients with BC meeting initial criteria, 1436 (7.5%) had a documented gBRCA test result. Among them, 10% had gBRCAm (n = 141, 43% hormone receptor positive [HR+], 57% triple-negative BC [TNBC]), 90% BRCAwt (n = 1294, 70% HR+, 30% TNBC), and 1 had a variant of uncertain significance. Median age at surgery was numerically lower in gBRCAm (43 years) than gBRCAwt (48 years) patients. Treatments included neoadjuvant-only therapy (gBRCAm 58%; gBRCAwt 34%), adjuvant-only therapy (gBRCAm 42%; gBRCAwt 66%) and both neoadjuvant and adjuvant therapy (gBRCAwt 0.1%). Median OS in both study cohorts was not reached. Median follow-up from surgery was less than 4 years (gBRCAm 47 months; gBRCAwt 46 months). At 48 months, estimated survival was 95% in gBRCAm and 94% in gBRCAwt patients. Conclusions: In this cohort of patients with HER2-negative eBC, among the 7.5% with a documented gBRCA result, 10% were identified with gBRCAm, reinforcing the need for gBRCA testing. Using structured real-world data through 2021 (prior to PARPi approval for eBC) with limited follow-up of &lt; 4 years, our study found that OS by gBRCA status was similar among patients with HER2-negative eBC. Our further research with chart review data containing granular clinical information looking at intermediate endpoints such as recurrence in eBC is under way.
Standardizing the strategy in glioblastoma trials to promote success in cell and gene therapy clinical development.
Authors: Izaskun Elorza, Damian Nirenberg, Martin Maczkiewicz, Floris Hoppener
Journal: Journal of Clinical Oncology (2023)

e13604 Background: Glioblastoma is the most common and aggressive brain tumor, with a high recurrence rate and low survival. We are increasing our understanding of its biology, and more targeted therapeutical agents are available. However, the GBM prognosis has not improved over the last decades. Multiple clinical trials on Cell and Gene Therapies are ongoing but, there is a huge need to define standardized and innovative strategies to promote better patient selection, implement adaptative designs and specific laboratory assays, and tailor the clinical endpoint assessments. Methods: Medical experts panel agreed on the following insights and gave advice to improve the design and conduct of GBM trials. Results: The criteria for selecting patients are not uniform among studies. The 2021 WHO Classification of central nervous system tumors has yet to be universally adopted, and different tumor entities are being treated as GBM according to the prior 2016 classification. Furthermore, the required genetic testing panel is only available in some countries as part of routine testing. A wide range of CGT therapies are being studied with different mechanisms of action and are well suited to be administered as combinatory regimens and multiple-dosing schedules to boost the antitumor effect. The implementation of master protocols offers the possibility to test different schedules to identify the most promising for further investigation during early phase development. There is a lack of biomarkers for the patient- or cancer-specific sensitivity and the efficacy of CGT. This is important not only to target clinical treatments to the appropriate patients and identify responding/non-responding patients early during treatment but also to improve the preclinical models and identify targets for further therapeutic development. Investigators should use standard endpoint criteria when reporting clinical outcomes. It has been common to refrain from introducing any preliminary-effect objective in the early stages. This tendency changes after guidance from experts and regulatory agencies about maximizing early-phase data. Another vital endpoint in the early phases is assessing patient immunogenicity against CG therapy based on humoral and cell virus-specific and tumor-specific immune responses. This is especially important as there are significant concerns in translating preclinical safety results to the clinic due to the species-specificity of different viruses and critical differences between immune systems. Conclusions: Today, the purpose of treatment for GBM is to extend the survival period and to manage the disease while preserving the patient’s quality of life. The goal of CGT is a durable complete response, but to achieve this target, we will need a deep analysis of how we perform clinical trials and move to an expert and tailored research environment.
Impact of race and age on intrinsic subtype distribution and treatment decisions in metastatic breast cancer: Preliminary analysis of HARMONY (LCCC1829).
Authors: Joannie M. Ivory, Naim Rashid, Paola Zagami, Charles M. Perou, Katherine Elizabeth Reeder-Hayes, Lisa A. Carey
Journal: Journal of Clinical Oncology (2023)

1055 Background: Gene expression profiling (GEP) is used to classify breast cancer (BC) into four intrinsic subtypes: Luminal A (LumA), Luminal B (LumB), HER2-Enriched, and Basal-like. Non-LumA subtypes are associated with poorer outcomes. Studies in early BC show that hormone receptor-positive (HR+)/HER2-negative (HER2-) tumors have a higher frequency of non-LumA subtypes in Black and younger (&lt;50) women. Similarly, triple negative BC, which carries the poorest prognosis and is mostly Basal-like, are overrepresented in Black and younger women. These variations in intrinsic subtype contribute to outcomes disparities. The extent to which these racial and age differences in subtypes and mortality occur in metastatic breast cancer (MBC) is unknown. Methods: HARMONY (NCT03769415) is a prospective clinical trial in patients with newly diagnosed MBC. Bulk tumor GEP (PAM50 intrinsic subtyping) is performed on primary and metastatic tumors. A primary objective is to determine the extent and treatment implications of molecular discordance (defined a priori as treatment differences by intrinsic subtype compared to clinical subtype); other endpoints to be reported later include GEP comparisons between primary and metastatic samples. Here we examine differences in a) intrinsic subtype and b) treatment patterns in MBC by race and age. Results: At the time of analysis, the study had accrued 220 participants. Mean age was 58, 24% were Black women. Sixty-five percent had HR+/HER2- MBC, 14% HER2-positive, and 21% triple negative. Unlike in early BC, LumB exceeded LumA (LumA 27%, LumB 35%, HER2-Enriched 12%, Basal-like 25%). Similar to early BC, subtype varied by race and age with more non-LumA subtypes in young and Black women. Discordance between intrinsic and clinical subtype was seen in 24% of Black, 20% of White women, in 29% of younger and 18% of older women. Treatment patterns also differed by race and age, where a higher percentage of younger Black women received first-line chemotherapy compared to younger White women overall (45% vs. 10%, p=0.0025), and in HR+/HER2- disease (33% vs 8.7%, p=&gt;0.05). No difference was seen in older women (24% vs 17%, p=0.44). Median progression free survival was worst in younger Black women compared to all other participants (5.4 vs 19.5 months, p=0.027), which may be driven by clinical subtype. Conclusions: Intrinsic subtype of tumors in a metastatic population has a different distribution by race and age than early BC, with more poor-prognosis non-LumA subtypes, and approximately 1 in 5 have discordance between clinical and molecular subtype, which may be therapeutically relevant. Clinical trial information: NCT03769415 . [Table: see text]
Neutrophil/lymphocyte ratio (NLR) and albumin-globulin ratio (AGR): Correlations with outcomes in patients with stage I-III breast cancer.
Authors: Min Li Tey, Siqin Zhou, Phyu Nitar, Hanis Mariyah Mohd Ishak, Christina Shi-Hui Yang, Grace Kusumawidjaja, Wen Yee Chay, Fuh-Yong Wong, Ru Xin Wong
Journal: Journal of Clinical Oncology (2023)

e12548 Background: The ratios of blood-based inflammatory biomarkers, such as NLR and AGR, have been found to correlate with outcomes in various malignancies. Higher NLR values reflect a pro-inflammatory state and are generally associated with worse outcomes. Conversely, higher AGR values reflect a fitter nutritional status and/or less chronic inflammation, and may hence be associated with better outcomes. We aim to investigate the association between NLR and AGR with survival among stage I-III breast cancer patients treated curatively, and with pathological complete response (pCR) rates among patients who have undergone neoadjuvant chemotherapy (NACT). Methods: A retrospective study of stage I-III breast cancer patients treated in a healthcare cluster in Singapore from 2011-2017 was performed. Clinical data was extracted from a prospectively maintained registry alongside full blood count (FBC) and liver function test (LFT) results. FBC and LFT were performed either 1-month pre-chemotherapy or pre-operatively. pCR is defined as stage ypT0/isN0M0 among patients who have undergone NACT. Optimal cut-offs for the NLR and AGR values are determined by maximal Youden’s Index for pCR, DFS and OS. Multivariate logistic regression, with NLR, AGR, age, stage, grade, and subtype, was used, with survival data between groups compared using the Cox regression analysis and log-rank tests. Results: A total of 1,188 patients were included in our study, with 323 patients receiving NACT, and 865 patients undergoing upfront surgery. On multivariable analysis of patients treated with NACT, higher AGR was associated with higher pCR (cutoff &gt;1.3, HR 2.0, p=0.02) and better DFS (&gt;1.6, HR 0.4, p=0.02) while a higher NLR with worse DFS (&gt;4.1, HR 1.8, p=0.03). In upfront surgery patients, higher AGR was associated with better OS (cutoff &gt;1.2, HR 0.5, p=0.00) while a higher NLR predicted for worse OS (&gt;2.4, HR 1.6, p=0.02). Conclusions: Inflammatory markers may be useful in predicting response to NACT and prognosticating survival. Larger studies should be undertaken to explore their value in clinical decision making. [Table: see text]
Prostate-specific membrane antigen (PSMA) expression in patients with metastatic triple negative breast cancer: Initial results of the PRISMA study.
Authors: Guilherme Nader Marta, Zena Wimana, Loubna Taraji, Gabriela Critchi, Philippe Georges Aftimos, Martine J. Piccart-Gebhart, Patrick Flamen, Geraldine Gebhart
Journal: Journal of Clinical Oncology (2023)

1025 Background: Radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA) prolongs survival of patients (pts) with prostate cancer. Preliminary immunohistochemistry (IHC)-based studies suggest that PSMA is highly expressed in triple negative breast cancer (TNBC). The PRISMA study aims to assess PSMA expression in pts with metastatic TNBC (mTNBC) via positron-emission tomography/computed tomography (PET/CT) to evaluate the feasibility of PSMA-targeted RLT for TNBC. Methods: PRISMA is a prospective, single-center study that enrolled pts with progressive mTNBC and measurable disease on 18 F-FDG PET/CT to undergo 68 Ga-PSMA-11 PET/CT. TNBC definition (ASCO/CAP) was based on the IHC of the primary breast cancer (BC) or metastasis. Target lesions (TL) were defined as metastatic lesions ≥1.5 cm with significant uptake in 18 FDG-PET/CT. The same TL regions were propagated to the 68 Ga-PSMA-PET/CT. 68 Ga-PSMA-11 maximum standard uptake value (SUV max ) was measured for each TL. PSMA patterns A and B were defined according to presence of a majority (pattern A) or a minority (pattern B) of positive TL on 68 Ga-PSMA (ie. uptake greater than that of normal liver parenchyma). Mann-Whitney U test was used to assess differences in median SUV max (mSUV max ) between subgroups. Results: Ten pts with progressive mTNBC were enrolled. One pt was excluded due to lack of TL on 18 FDG-PET/CT. Median age was 48 years (range 36-68), median number of TL per patient was 8 (5-18). Five pts had a TNBC IHC since the initial BC diagnosis, while 4 had a switch to TNBC (4 with initial estrogen receptor [ER]-positive and 1 with HER2-positive BC). All evaluable pts had inter- and intra-organ heterogeneity in PSMA uptake in TL and 2 pts had some mismatch with FDG-positive and PSMA-negative TL. mSUV max was 2.99 (range 1.7-6.3) in the overall population and was higher in pts with pattern A (5.1 vs 2.6 in patterns A and B, respectively, p = 0.03). mSUVmax was numerically higher in younger pts (5.0 vs 2.6 in pts &lt;50y and ≥50y, p = 0.28), PD-L1-positive (5.0 vs 2.7 in PD-L1-positive and -negative, p = 0.14), de novo metastatic disease (5.0 vs 2.9 in de novo and recurrent BC, p = 0.38) and those with ER-negative primary breast tumor (3.4 vs 3.0 in ER-negative and ER-positive primary BC, p = 0.9). Conclusions: A significant PSMA uptake was observed in a proportion of pts with mTNBC. Inclusion of additional pts and translational analyses will allow the identification of PSMA expression determinants. PSMA-targeted RLT may be considered as an innovative therapeutic strategy to be explored in selected pts with mTNBC. [Table: see text]
Extracellular vesicle-derived non-coding RNAs to predict outcome in patients with triple-negative breast cancer (TNBC) with residual disease (RD).
Authors: Shane R Stecklein, Devin Koestler, Nanda K Yellapu, Rachel Yoder, Bruce F. Kimler, Joshua M. Staley, Zachary Schmitt, Qamar J. Khan, Anne O'Dea, Lauren Elizabeth Nye, Manana Elia, Jaimie Heldstab, Trisha Home, Stephen Hyter, Kamilla Isakova, Harsh B Pathak, Andrew K. Godwin, Priyanka Sharma
Journal: Journal of Clinical Oncology (2023)

578 Background: TNBC patients with RD after neoadjuvant systemic therapy (NAST) have high risk of recurrence. Biomarkers to risk-stratify patients with RD could individualize adjuvant therapy and inform adjuvant therapy trials. We aim to investigate the impact of circulating extracellular vesicle (EV)-derived non-coding RNAs (exo-ncRNAs) on outcomes in TNBC patients with RD. Methods: The study population included 79 TNBC patients with RD post-NAST and available end-of- treatment plasma samples enrolled in an IRB-approved multisite prospective registry. EVs and their associated exo-ncRNAs were isolated by membrane affinity spin columns (Qiagen exoRNeasy). Exo-ncRNA was subjected to next-generation sequencing (Qiagen QIAseq miRNA library kit). N=47 served as a discovery cohort and N=32 served as validation cohort. With inclusion of transcripts expressed in ≥ 80% of samples, there were 1,123 normalized reads/sample. Hazard ratios and C-statistics for event-free survival (EFS) were computed for each exo-ncRNA. We report exo-ncRNAs that were significantly associated with EFS in both the discovery and validation cohorts. Results: Patient and tumor characteristics were balanced in discovery and validation cohorts. Three exo-ncRNAs were associated with increased recurrence risk in both the discovery dataset ( miR-200a-3p, HR=1.39, 95%CI 1.01-1.89, P=0.04, C-stat=0.55; miR-203a-3p, HR=1.77, 95%CI 1.15-2.73, P=0.01, C-stat=0.59; and miR-7845-5p, HR=1.53, 95%CI 1.15-2.05, P=0.004, C-stat=0.62) and the validation dataset ( miR-200a-3p, HR=1.83, 95%CI 1.24-2.72, P=0.003, C-stat=0.76; miR-203a-3p, HR=1.78, 95%CI 1.10-2.87, P=0.02, C-stat=0.67; and miR-7845-5p, HR=2.06, 95%CI 1.06-4.01, P=0.03, C-stat=0.52). Using the miRNA Target Prediction Database (miRDB), we identified 1,088, 1,352, and 387 predicted targets for miR-200a-3p, miR-203a-3p, and miR-7845-5p, respectively. Amongst 2,827 prediction events there were 2,526 unique target mRNAs. 2,235 mRNAs were targets for one candidate miRNAs, 281 mRNAs were predicted targets for two candidate miRNAs, and 10 mRNAs were predicted as targets for all three candidate miRNAs. Conclusions: The expression of miR-200a-3p, miR-203a-3p, and miR-7845-5p in plasma-derived EVs in TNBC patients with RD after NAST is associated with increased risk of recurrence. We identified ten mRNAs that are predicted targets of all three of these miRNAs. If validated in additional cohorts these exo-ncRNAs could be used in a liquid-biopsy assay to identify high-risk patients with RD who could benefit from adjuvant treatment intensification. [Table: see text]